Microinjection of carbachol in the supramammillary region suppresses CA1 pyramidal cell synaptic excitability

Previous studies have established that the posterior hypothalamus-supramammillary (SUM) region is involved in the control of the hippocampal theta rhythm and also modulates the synaptic excitation of hippocampal neurons. Particularly, the medial but not lateral SUM region mediates reticular stimulation-induced suppression of CA1 pyramidal cell synaptic excitation to Schaffer collateral stimulation. In the present study using urethane anesthetized rats, we have investigated the effect of direct chemical stimulation of the posterior hypothalamus-SUM region on CA1 pyramidal cell excitability. It was observed that microinjection of the cholinergic muscarinic receptor agonist, carbachol (0.1 microl, concentration of either 0.0052, 0.156, or 0.625 microg/microl), evoked concentration-dependent suppression of CA1 pyramidal cell excitability that was dissociated from theta activation. Further, carbachol microinjection preferentially recruited the lateral SUM region when compared with the medial SUM and the posterior hypothalamic regions. In this context, the shortest latencies to suppression at the lowest concentration of carbachol and the strongest suppression at higher concentrations were observed with lateral microinjections. The carbachol-induced suppression was attenuated by inactivation of the medial septal region by microinjection of procaine (0.5 microl, 20% w/v). These results underscore a possible role for cholinergic mechanisms in the lateral SUM region in modulation of CA1 pyramidal cell synaptic excitation via the medial septal region. Furthermore, the present findings when juxtaposed with the medial SUM mediation of reticularly-elicited suppression suggest a medial-lateral topographic organization of the SUM region in modulation of CA1 excitability.